Pre-eclampsia
Pre-eclampsia is a multisystem disorder of pregnancy characterized by new-onset hypertension (≥140/90 mmHg) and proteinuria (≥0.3g/24h or PCR ≥30 mg/mmol) or end-organ dysfunction developing after 20 weeks gestation in a previously normotensive woman. It affects 2-8% of pregnancies worldwide and is a leading cause of maternal and perinatal morbidity and mortality. The condition results from abnormal placentation leading to widespread endothelial dysfunction, affecting multiple organ systems including the kidneys, liver, brain, and cardiovascular system. The only definitive cure is delivery of the placenta, making timing of delivery a critical clinical decision balancing maternal safety against fetal prematurity risks.
Key Facts:
- Definition: Hypertension ≥140/90 mmHg + proteinuria or end-organ dysfunction after 20 weeks
- Prevalence: 2-8% of pregnancies globally
- Incidence: 3-5% in developed countries, higher in developing countries
- Mortality: Leading cause of maternal death in developed countries (10-15% of maternal deaths)
- Morbidity: Significant maternal and perinatal complications
- Peak Demographics: Primigravidas, age extremes (less than 20 or >40 years)
- Pathognomonic Feature: New-onset hypertension + proteinuria after 20 weeks
- Gold Standard Investigation: Urine protein:creatinine ratio (PCR) ≥30 mg/mmol
- First-line Treatment: Blood pressure control, magnesium sulfate for seizure prophylaxis, delivery
- Prognosis Summary: Excellent with timely diagnosis and management; poor if untreated
Clinical Pearls:
The "Silent Killer": Many women feel completely fine despite a BP of 180/120. Do not rely on symptoms. Any headache or visual disturbance in pregnancy is Pre-eclampsia until proven otherwise.
Magnesium is Magic: Magnesium Sulphate is the drug of choice for preventing and treating Eclamptic seizures. It is a vasodilator and membrane stabilizer. Diazepam is NOT effective for eclampsia.
Epigastric Pain: This is a grave sign. It represents subcapsular liver haematoma/oedema (Glisson's capsule stretch). It often precedes rupture or seizure. Never dismiss it as "heartburn".
PlGF Testing: Placental Growth Factor (PlGF) has high negative predictive value. If PlGF is normal, it is very unlikely the woman will need delivery for PE in the next 14 days. Allows safe discharge.
Fluid Restriction: In PE, the endothelium is leaky. If you give normal fluids (e.g. 125ml/hr), it leaks into the lungs causing flash pulmonary oedema. Restrict to 80ml/hr.
Why This Matters Clinically: Pre-eclampsia is a leading cause of maternal mortality worldwide, accounting for 10-15% of maternal deaths in developed countries and up to 25% in developing countries. It is associated with significant perinatal morbidity including preterm birth, intrauterine growth restriction, and stillbirth. Early recognition and appropriate management can prevent severe complications including eclampsia, HELLP syndrome, stroke, and maternal death. The condition has long-term implications, with affected women having increased risk of cardiovascular disease, hypertension, and stroke later in life. Medico-legally, failure to recognize and appropriately manage pre-eclampsia is a common cause of litigation, particularly when eclampsia occurs or when delivery is delayed inappropriately.
Incidence & Prevalence:
- Incidence: 3-5% of pregnancies in developed countries, 5-8% in developing countries
- Prevalence: 2-8% of all pregnancies globally
- Lifetime Risk: Approximately 5-10% for women with one pregnancy
- Trend: Relatively stable, though increasing due to rising maternal age and obesity
- Geographic Variation: Higher in developing countries, lower in developed countries with good antenatal care
- Temporal Trends: No significant seasonal variation
Demographics:
| Factor | Details | Clinical Significance |
|---|---|---|
| Age | Peak: 20-35 years; Higher risk less than 20 or >40 years | Extremes of age associated with poor placentation |
| Sex | Female only (pregnancy-specific) | Hormonal and immunological factors |
| Parity | Primigravidas: 3-5x higher risk | Lack of prior exposure to paternal antigens |
| Ethnicity | Higher in Black, Hispanic, South Asian women | Genetic and socioeconomic factors |
| Geography | Higher in developing countries | Access to care, nutrition, healthcare quality |
| Socioeconomic | Higher in lower socioeconomic groups | Access to care, nutrition, comorbidities |
| BMI | Obesity (BMI >30): 2-3x increased risk | Metabolic and inflammatory factors |
Risk Factors:
Non-Modifiable Risk Factors:
| Factor | Relative Risk (95% CI) | Mechanism |
|---|---|---|
| Age >40 years | RR 1.5-2.0 (1.2-2.5) | Reduced uterine perfusion, comorbidities |
| Age less than 20 years | RR 1.3-1.8 (1.1-2.2) | Immature reproductive system |
| Primigravida | RR 3.0-5.0 (2.5-6.0) | Lack of prior exposure to paternal antigens |
| Family history | RR 2.0-3.0 (1.5-4.0) | Genetic predisposition |
| Previous pre-eclampsia | RR 7.0-10.0 (5.0-15.0) | Recurrence risk, underlying predisposition |
| Black ethnicity | RR 1.5-2.0 (1.2-2.5) | Genetic and socioeconomic factors |
| Multiple pregnancy | RR 2.0-3.0 (1.5-4.0) | Increased placental mass, higher metabolic demand |
Modifiable Risk Factors:
| Risk Factor | Relative Risk (95% CI) | Evidence Level | Intervention Impact |
|---|---|---|---|
| Obesity (BMI >30) | RR 2.0-3.0 (1.5-4.0) | Level 1a | 20-30% reduction with weight loss |
| Chronic hypertension | RR 5.0-10.0 (4.0-15.0) | Level 1a | Control reduces severity |
| Diabetes (Type 1/2) | RR 2.0-4.0 (1.5-6.0) | Level 1a | Good glycemic control reduces risk |
| Chronic kidney disease | RR 4.0-8.0 (3.0-12.0) | Level 1b | Preconception optimization |
| Autoimmune disease (SLE) | RR 3.0-5.0 (2.0-7.0) | Level 1b | Disease control reduces risk |
| Smoking | RR 0.5-0.7 (0.3-0.9) | Level 1a | Protective (but harmful overall) |
| Aspirin prophylaxis | RR 0.6-0.8 (0.5-0.9) | Level 1a | 20-40% reduction if high risk |
Protective Factors:
- Aspirin 150mg daily from 12 weeks: 20-40% reduction in high-risk women (ASPRE trial)
- Smoking: Paradoxically protective (RR 0.5-0.7) but overall harmful
- Previous normal pregnancy: Reduces risk in subsequent pregnancies
Mechanism (Two-Stage Theory):
Step 1: Poor Placentation (First Trimester)
- Trophoblast Invasion: Normal pregnancy requires extravillous trophoblast cells to invade the maternal spiral arteries, transforming them from high-resistance to low-resistance vessels
- Failure in Pre-eclampsia: In pre-eclampsia, trophoblast invasion is shallow and incomplete
- Spiral Arteries: Remain narrow, high-resistance vessels instead of becoming wide, low-resistance channels
- Mechanism: Abnormal immune tolerance, genetic factors, or environmental factors prevent proper invasion
- Time Course: Occurs in first trimester, but clinical disease manifests later
- Reversibility: Not reversible once established, but progression can be modified
Step 2: Placental Ischaemia (Second Trimester)
- Reduced Perfusion: Narrow spiral arteries cannot provide adequate blood flow to placenta
- Hypoxia: Placenta becomes relatively hypoxic and ischaemic
- Oxidative Stress: Ischaemia-reperfusion injury leads to oxidative stress
- Soluble Factors: Placenta releases anti-angiogenic factors into maternal circulation:
- sFlt-1 (soluble Fms-like tyrosine kinase-1): Binds and inactivates VEGF and PlGF
- sEng (soluble endoglin): Inhibits TGF-β signaling
- Inflammatory Cytokines: TNF-α, IL-6, IL-8
- Time Course: Progressive throughout second and third trimesters
- Clinical Correlation: May be detected by low PlGF levels before clinical disease
Step 3: Endothelial Dysfunction (Third Trimester)
- Systemic Effects: Anti-angiogenic factors cause widespread maternal endothelial dysfunction
- Vasoconstriction: Loss of vasodilatory capacity, increased vascular tone
- Increased Permeability: Endothelial barrier function impaired, allowing protein leakage
- Procoagulant State: Endothelial activation promotes thrombosis
- Organ-Specific Effects:
- Kidney: Glomerular endotheliosis → proteinuria, reduced GFR
- Liver: Sinusoidal obstruction → elevated transaminases, HELLP syndrome
- Brain: Cerebral oedema, vasospasm → headache, visual disturbance, seizures
- Cardiovascular: Increased afterload, reduced cardiac output
- Platelets: Consumption, activation → thrombocytopenia
- Time Course: Develops over days to weeks
- Point of No Return: Severe endothelial damage may be irreversible without delivery
Step 4: Clinical Manifestation
- Hypertension: Vasoconstriction and increased vascular resistance
- Proteinuria: Glomerular damage allows protein leakage
- End-Organ Dysfunction: Multiple systems affected
- Progression: Can progress rapidly to severe disease
- Factors Accelerating Progression:
- Severe hypertension
- Early onset (less than 34 weeks)
- Multiple risk factors
- Poor antenatal care
Step 5: Resolution or Complications
- Delivery: Removal of placenta removes source of anti-angiogenic factors
- Recovery: Endothelial function gradually returns to normal (days to weeks)
- Chronic Damage: Some women have persistent endothelial dysfunction
- Long-term Risk: Increased cardiovascular risk later in life
- Factors Affecting Outcome:
- Severity of disease
- Timing of delivery
- Quality of management
- Underlying comorbidities
Classification:
Mild Pre-eclampsia:
- BP 140-159/90-109 mmHg
- Proteinuria present (PCR ≥30 mg/mmol)
- No end-organ dysfunction
- Usually managed as outpatient with close monitoring
Severe Pre-eclampsia:
- BP ≥160/110 mmHg, OR
- Severe proteinuria (PCR ≥100 mg/mmol), OR
- End-organ dysfunction:
- Renal: Creatinine >90 μmol/L, oliguria
- Hepatic: Elevated transaminases, epigastric pain
- Neurological: Headache, visual disturbance, clonus
- Haematological: Thrombocytopenia less than 100 x 10⁹/L
- Pulmonary: Oedema
- Requires inpatient management and delivery planning
Eclampsia:
- Pre-eclampsia + seizures
- Can occur antepartum, intrapartum, or postpartum (up to 6 weeks)
- 44% of eclamptic seizures occur postpartum
- Medical emergency requiring immediate treatment
HELLP Syndrome:
- Haemolysis (schistocytes, elevated LDH)
- Elevated Liver enzymes (ALT/AST)
- Low Platelets (less than 100 x 10⁹/L)
- Variant of severe pre-eclampsia
- High morbidity and mortality
Symptoms:
Typical Presentation:
Atypical Presentations:
Signs:
Hypertension:
Neurological:
Abdominal:
Cardiovascular:
Red Flags:
[!CAUTION] Red Flags — Seek immediate help if:
- Severe hypertension (≥160/110 mmHg)
- Eclampsia (seizures)
- HELLP Syndrome (haemolysis, elevated LFTs, low platelets)
- Epigastric/RUQ pain (liver capsule stretch)
- Papilloedema or clonus (cerebral irritation)
- Visual disturbance (scintillating scotomata)
- Persistent headache not relieved by paracetamol
- Reduced fetal movements
- Signs of placental abruption
Structured Approach:
General:
- Appearance: May look well despite severe hypertension ("silent killer")
- Vital Signs:
- BP: Measure with appropriate cuff, both arms
- Heart rate: May be elevated
- Respiratory rate: May be elevated if pulmonary oedema
- Temperature: Usually normal (fever suggests infection)
- Weight: Rapid weight gain may indicate fluid retention
Cardiovascular:
- BP Measurement:
- Use correct cuff size
- Measure in sitting position, arm at heart level
- Repeat if elevated
- Check both arms (difference may indicate aortic dissection)
- Heart Sounds: Usually normal, may have S3 if heart failure
- JVP: Usually normal, elevated if heart failure
- Peripheral Oedema: Face, hands, legs (pedal oedema alone is normal)
Abdominal:
- Inspection: May show distension if ascites
- Palpation:
- Epigastric/RUQ tenderness (liver involvement, HELLP)
- Uterine size (may be small for dates if IUGR)
- Fetal movements
- Auscultation: Fetal heart rate monitoring
Neurological:
- Mental State: Usually normal, may be altered in severe disease
- Cranial Nerves: Usually normal, visual field defects possible
- Reflexes:
- Hyperreflexia (>3+)
- Clonus: Test at ankle, >3 beats is significant
- Fundoscopy:
- Papilloedema (severe disease)
- Retinal changes (hypertensive retinopathy)
- Coordination: Usually normal
Special Tests:
| Test | Technique | Positive Finding | Clinical Significance |
|---|---|---|---|
| Clonus Test | Rapid dorsiflexion of foot | >3 beats of clonus | Imminent seizure risk |
| Reflexes | Standard deep tendon reflexes | Hyperreflexia (>3+) | Neurological irritability |
| Fundoscopy | Direct ophthalmoscopy | Papilloedema, retinal changes | Severe disease, cerebral oedema |
| Epigastric Tenderness | Deep palpation RUQ | Tenderness, guarding | Liver involvement, HELLP risk |
| Urine Dipstick | Standard urinalysis | Protein 1+ or more | Needs quantification (PCR) |
First-Line (Bedside):
- BP Measurement: Essential, use appropriate cuff size
- Urinalysis: Protein dipstick (1+ needs quantification)
- Fetal Heart Rate: Continuous monitoring if severe
Laboratory Tests:
| Test | Expected Finding | Purpose |
|---|---|---|
| Urine PCR | ≥30 mg/mmol (mild), ≥100 mg/mmol (severe) | Confirms proteinuria, quantifies severity |
| PlGF | Low (less than 100 pg/ml) indicates placental dysfunction | Rule out pre-eclampsia, predict need for delivery |
| FBC | Thrombocytopenia (less than 150 x 10⁹/L), may be less than 100 in HELLP | Assess for HELLP, DIC risk |
| U&E | Creatinine >90 μmol/L (renal dysfunction), Urate elevated | Assess renal function, severity marker |
| LFT | ALT/AST elevated (HELLP), Bilirubin elevated if haemolysis | Assess liver function, diagnose HELLP |
| LDH | Elevated in HELLP (haemolysis marker) | Diagnose HELLP |
| Coagulation | May be deranged in severe disease/DIC | Assess coagulation status |
| sFlt-1/PlGF Ratio | Elevated ratio indicates pre-eclampsia | Diagnostic and prognostic marker |
Imaging:
| Modality | Findings | Indication |
|---|---|---|
| Ultrasound (Fetal) | IUGR, oligohydramnios, abnormal Dopplers | Assess fetal wellbeing, growth |
| Ultrasound (Maternal) | Liver haematoma, ascites | If HELLP suspected, epigastric pain |
| CT Head | Cerebral oedema, haemorrhage | If neurological symptoms, eclampsia |
| MRI Head | More sensitive for cerebral changes | If CT normal but high suspicion |
| Chest X-ray | Pulmonary oedema | If respiratory symptoms |
Diagnostic Criteria (ISSHP 2014):
- Hypertension (≥140/90 mmHg) developing after 20 weeks
- AND one of:
- Proteinuria (≥0.3g/24h or PCR ≥30 mg/mmol), OR
- End-organ dysfunction:
- Renal: Creatinine >90 μmol/L, oliguria
- Hepatic: Elevated transaminases, severe RUQ pain
- Neurological: Headache, visual disturbance, clonus
- Haematological: Thrombocytopenia, haemolysis
- Pulmonary: Oedema
Management Algorithm:
PRE-ECLAMPSIA DIAGNOSED
(BP ≥140/90 + PCR ≥30)
↓
ASSESS SEVERITY
┌────────┴────────┐
MILD/MODERATE SEVERE
(140-159/90-109) (≥160/110 or
end-organ dysfunction)
↓ ↓
OUTPATIENT INPATIENT
MONITORING MANAGEMENT
↓ ↓
ORAL ANTI- IV ANTI-HYPERTENSIVES
HYPERTENSIVES - Labetalol IV
- Labetalol - Hydralazine IV
- Nifedipine MR - Nifedipine PO
↓ ↓
MONITOR MAGNESIUM SULFATE
- BP 2-3x/week - 4g IV loading
- Urine PCR - 1g/hr infusion
- Fetal scans - Monitor reflexes
↓ ↓
PLAN DELIVERY FLUID RESTRICTION
- Usually 37wks - 80ml/hr (prevent
- Earlier if pulmonary oedema)
worsening ↓
STEROIDS
(If less than 34 weeks)
- Betamethasone
12mg IM x2
24h apart
↓
DELIVERY
- Stabilize first
- Then induce/CS
- Timing depends on
gestation, severity
Acute/Emergency Management:
Immediate Actions (Severe Pre-eclampsia):
- ABC: Assess airway, breathing, circulation
- IV Access: Large bore cannula
- Monitor: Continuous BP, pulse oximetry, fetal heart rate
- Control BP: IV labetalol or hydralazine to target less than 160/110
- Magnesium Sulfate: If severe or eclampsia (4g IV loading, then 1g/hr)
- Fluid Restriction: 80ml/hr to prevent pulmonary oedema
- Catheterize: Monitor urine output
- Delivery Planning: Urgent delivery usually required
Conservative Management:
Mild Pre-eclampsia:
- Outpatient Monitoring:
- BP checks 2-3 times per week
- Urine PCR weekly
- Fetal growth scans every 2-3 weeks
- Fetal Dopplers if IUGR suspected
- Lifestyle:
- Rest (left lateral position)
- No salt restriction (not helpful)
- Regular antenatal appointments
- Delivery: Usually at 37 weeks, earlier if worsening
Medical Management:
| Drug Class | Drug | Dose | Route | Duration | Notes |
|---|---|---|---|---|---|
| Alpha/Beta Blocker | Labetalol | 100-200mg BD-TDS | PO | Until delivery | First line, avoid in asthma |
| Calcium Channel Blocker | Nifedipine MR | 20-40mg BD | PO | Until delivery | Second line, modified release |
| Central Alpha Agonist | Methyldopa | 250mg-1g TDS | PO | Until delivery | Third line, sedating |
| Alpha/Beta Blocker | Labetalol | 20mg IV bolus, then 20-80mg/hr | IV | Acute control | For severe hypertension |
| Direct Vasodilator | Hydralazine | 5-10mg IV bolus, repeat | IV | Acute control | Alternative to labetalol |
| Anticonvulsant | Magnesium Sulfate | 4g IV loading (10-15min), then 1g/hr | IV | 24-48h or until 24h post-delivery | For severe PE/eclampsia |
| Corticosteroid | Betamethasone | 12mg IM x2, 24h apart | IM | Single course | If less than 34 weeks for fetal lung maturity |
Contraindications:
- ACE Inhibitors/ARBs: Teratogenic, cause renal failure in fetus
- Beta-blockers alone: May cause bradycardia, avoid in asthma
- Diuretics: Not recommended (already volume contracted)
Surgical Management:
Delivery Indications:
- Severe pre-eclampsia at any gestation (after stabilization)
- Mild pre-eclampsia at 37 weeks
- Deteriorating maternal condition
- Fetal compromise
- Eclampsia (after seizure control)
- HELLP syndrome
Delivery Methods:
- Induction of Labour: If >34 weeks, favorable cervix, no fetal compromise
- Caesarean Section: If less than 34 weeks, unfavorable cervix, fetal compromise, or maternal instability
Disposition:
- Admit if: Severe pre-eclampsia, symptoms, or concerns about fetal wellbeing
- Discharge if: Mild pre-eclampsia, well-controlled BP, good fetal growth, reliable follow-up
- Follow-up:
- Mild: 2-3 times per week
- Severe: Daily or more frequent
- Postpartum: 6 weeks, then annual cardiovascular risk assessment
Immediate (Minutes-Hours):
| Complication | Incidence | Presentation | Management |
|---|---|---|---|
| Eclampsia | 1-2% of pre-eclampsia | Seizures (tonic-clonic), 44% postpartum | Magnesium sulfate, delivery |
| HELLP Syndrome | 10-20% of severe PE | RUQ pain, elevated LFTs, low platelets | Delivery, supportive care |
| Stroke | 1-2% of severe PE | Neurological deficit, headache | BP control, neuroimaging, delivery |
| Pulmonary Oedema | 2-5% of severe PE | Dyspnoea, hypoxia, crackles | Diuretics, oxygen, fluid restriction |
| Placental Abruption | 1-2% | Vaginal bleeding, abdominal pain, fetal distress | Emergency delivery |
| Renal Failure | 1-2% of severe PE | Oliguria, rising creatinine | Fluid management, delivery, may need dialysis |
Early (Days):
Maternal:
- Persistent Hypertension: May require ongoing treatment
- Proteinuria: Usually resolves within weeks
- Thrombocytopenia: Usually resolves within days
- Liver Dysfunction: Usually resolves within weeks
Fetal:
- Preterm Birth: Common, associated with complications
- Intrauterine Growth Restriction: Due to placental dysfunction
- Stillbirth: Risk increased if severe, untreated
- Neonatal Complications: Respiratory distress, hypoglycaemia, jaundice
Late (Weeks-Months):
Maternal:
- Persistent Hypertension: 20-30% develop chronic hypertension
- Chronic Kidney Disease: Rare, but risk increased
- Cardiovascular Disease: 2-3x increased risk long-term
- Recurrence: 15% overall, up to 50% if severe/early
Fetal/Child:
- Neurodevelopmental: Slight increase in risk if very preterm
- Cardiovascular: Increased risk of hypertension, metabolic syndrome
Natural History:
- Untreated: Progressive worsening, high risk of eclampsia, HELLP, stroke, maternal and fetal death
- Mild, Treated: Usually good outcome, delivery at term
- Severe, Treated: Good outcome with timely delivery, but prematurity risks
Outcomes with Treatment:
| Variable | Outcome |
|---|---|
| Maternal Mortality | less than 1% with treatment, 10-15% if untreated |
| Eclampsia | 1-2% with treatment, 5-10% if untreated |
| HELLP Syndrome | 10-20% of severe cases |
| Fetal/Perinatal Mortality | 1-2% with treatment, 10-20% if untreated |
| Preterm Birth | 15-20% overall, higher if severe |
| Recurrence | 15% overall, 50% if severe/early |
| Long-term Hypertension | 20-30% develop chronic hypertension |
| Cardiovascular Disease | 2-3x increased risk long-term |
Prognostic Factors:
Good Prognosis:
- Mild disease, late onset (>37 weeks)
- Good BP control
- No end-organ dysfunction
- Good fetal growth
- Reliable follow-up and compliance
Poor Prognosis:
- Severe disease, early onset (less than 34 weeks)
- HELLP syndrome
- Eclampsia
- End-organ dysfunction
- Poor fetal growth
- Multiple risk factors
- Limited access to care
Key Guidelines:
-
NICE NG133 (2019) — Hypertension in pregnancy: diagnosis and management. Key recommendations: BP target less than 135/85, aspirin prophylaxis for high-risk women, PlGF testing. NICE
-
RCOG Green-top Guideline No. 10A (2010) — Management of Severe Pre-eclampsia/Eclampsia. Key recommendations: Magnesium sulfate protocols, delivery timing. RCOG
-
ISSHP (2014) — The classification, diagnosis and management of the hypertensive disorders of pregnancy. Key recommendations: Updated diagnostic criteria, classification. PMID: 24785617
-
ACOG Practice Bulletin No. 222 (2020) — Gestational Hypertension and Preeclampsia. Key recommendations: Diagnosis, management, delivery timing. ACOG
Landmark Trials:
1. ASPRE Trial (2017) — Aspirin versus Placebo in Pregnancies at High Risk for Preterm Preeclampsia
- 1,776 women at high risk
- Key finding: Aspirin 150mg from 11-14 weeks reduced preterm pre-eclampsia by 62% (1.6% vs 4.3%, pless than 0.001)
- Clinical Impact: Established aspirin prophylaxis for high-risk women, changed practice worldwide
- PMID: 28741785
2. Magpie Trial (2002) — Do women with pre-eclampsia, and their babies, benefit from magnesium sulphate?
- 10,141 women with pre-eclampsia
- Key finding: Magnesium sulfate reduced risk of eclampsia by 58% (0.8% vs 1.9%, RR 0.42, 95% CI 0.29-0.60)
- Clinical Impact: Established magnesium sulfate as standard of care for severe pre-eclampsia/eclampsia
- PMID: 12057549
3. CLASP Trial (1995) — Collaborative Low-dose Aspirin Study in Pregnancy
- 9,364 women
- Key finding: Low-dose aspirin (60mg) did not significantly reduce pre-eclampsia in unselected women
- Clinical Impact: Led to targeted aspirin use in high-risk women only
- PMID: 7474196
4. PARIS Trial (2007) — Postpartum Aspirin to Reduce Recurrence
- Smaller trial
- Key finding: Postpartum aspirin may reduce recurrence risk
- Clinical Impact: Ongoing research area
Evidence Strength:
| Intervention | Level | Key Evidence |
|---|---|---|
| Aspirin Prophylaxis | 1a | ASPRE trial, multiple meta-analyses |
| Magnesium Sulfate | 1a | Magpie trial, Cochrane review |
| BP Control | 1b | Multiple RCTs, observational studies |
| Delivery Timing | 2a | Observational studies, expert consensus |
| PlGF Testing | 1b | Multiple diagnostic studies |
Systematic Reviews:
- Duley L, et al. Magnesium sulphate and other anticonvulsants for women with pre-eclampsia. Cochrane Database Syst Rev. 2010;(11):CD000025. PMID: 21069663
- Roberge S, et al. Aspirin for the prevention of pre-eclampsia. Cochrane Database Syst Rev. 2018;(10):CD004659. PMID: 30351470
What is Pre-eclampsia? Pre-eclampsia is a condition that can happen in pregnancy where your blood pressure goes up and your kidneys start leaking protein into your urine. It usually starts after 20 weeks of pregnancy. It happens because the placenta (the organ that feeds your baby) doesn't grow into your womb properly, which causes problems throughout your body.
Why does it matter? If not treated, pre-eclampsia can be very dangerous for both you and your baby. It can cause:
- Seizures (fits) called eclampsia
- Problems with your liver and blood
- Strokes
- Your baby not growing properly
- Premature birth
- In very severe cases, it can be life-threatening
How is it treated?
- Blood Pressure Medicines: We give you medicines to lower your blood pressure and keep you safe
- Magnesium: If it's severe, we give you magnesium through a drip to prevent seizures
- Monitoring: We check you and your baby closely, often in hospital
- Delivery: The only way to completely cure it is to deliver your baby. We might need to do this early if you or your baby are at risk
What to expect:
- You'll need more frequent check-ups
- You might need to stay in hospital
- We'll monitor your blood pressure and do blood and urine tests
- We'll check your baby's growth with scans
- You might need to have your baby early (before your due date)
- After delivery, you'll usually get better within days to weeks
- You'll need follow-up to check your blood pressure
When to seek help: Call your midwife or go to hospital immediately if you have:
- A very bad headache that won't go away with paracetamol
- Problems with your vision (flashing lights, blurring)
- Pain in the top of your tummy (epigastric pain)
- Swelling of your face or hands that came on quickly
- Your baby moving less than usual
- Any concerns about your health or your baby
Primary Guidelines:
-
National Institute for Health and Care Excellence. Hypertension in pregnancy: diagnosis and management (NG133). 2019. NICE
-
Royal College of Obstetricians and Gynaecologists. Management of Severe Pre-eclampsia/Eclampsia (Green-top Guideline No. 10A). 2010. RCOG
-
Brown MA, Magee LA, Kenny LC, et al. The hypertensive disorders of pregnancy: ISSHP classification, diagnosis & management recommendations for international practice. Pregnancy Hypertens. 2018;13:291-310. PMID: 29803330
-
American College of Obstetricians and Gynecologists. Gestational Hypertension and Preeclampsia: ACOG Practice Bulletin, Number 222. Obstet Gynecol. 2020;135(6):e237-e260. PMID: 32443079
Landmark Trials:
-
Rolnik DL, Wright D, Poon LC, et al. Aspirin versus Placebo in Pregnancies at High Risk for Preterm Preeclampsia. N Engl J Med. 2017;377(7):613-622. PMID: 28741785
-
Altman D, Carroli G, Duley L, et al. Do women with pre-eclampsia, and their babies, benefit from magnesium sulphate? The Magpie Trial: a randomised placebo-controlled trial. Lancet. 2002;359(9321):1877-1890. PMID: 12057549
-
Duley L, Gülmezoglu AM, Henderson-Smart DJ, et al. Magnesium sulphate and other anticonvulsants for women with pre-eclampsia. Cochrane Database Syst Rev. 2010;(11):CD000025. PMID: 21069663
-
CLASP (Collaborative Low-dose Aspirin Study in Pregnancy) Collaborative Group. CLASP: a randomised trial of low-dose aspirin for the prevention and treatment of pre-eclampsia among 9364 pregnant women. Lancet. 1994;343(8898):619-629. PMID: 7474196
-
Magpie Trial Follow-Up Study Collaborative Group. The Magpie Trial: a randomised trial comparing magnesium sulphate with placebo for pre-eclampsia. Outcome for women at 2 years. BJOG. 2007;114(3):300-309. PMID: 17166220
Systematic Reviews & Meta-Analyses:
-
Roberge S, Nicolaides K, Demers S, et al. The role of aspirin dose on the prevention of preeclampsia and fetal growth restriction: systematic review and meta-analysis. Am J Obstet Gynecol. 2017;216(2):110-120.e6. PMID: 27780739
-
Duley L, Henderson-Smart DJ, Walker GJ, et al. Magnesium sulphate versus diazepam for eclampsia. Cochrane Database Syst Rev. 2010;(12):CD000127. PMID: 21154341
-
Chappell LC, Duckworth S, Seed PT, et al. Diagnostic accuracy of placental growth factor in women with suspected preeclampsia: a prospective multicenter study. Circulation. 2013;128(20):2121-2131. PMID: 24048186
Additional References:
-
Shen L, Martinez-Portilla RJ, Rolnik DL, et al. ASPRE trial: risk factors for development of preterm pre-eclampsia despite aspirin prophylaxis. Ultrasound Obstet Gynecol. 2021;58(5):710-716. PMID: 33998099
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Rolnik DL, Syngelaki A, O'Gorman N, et al. Aspirin for evidence-based preeclampsia prevention trial: effects of aspirin on maternal serum pregnancy-associated plasma protein A and placental growth factor trajectories in pregnancy. Am J Obstet Gynecol. 2024;230(3):347.e1-347.e14. PMID: 38151219
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Hauspurg A, Jeyabalan A. Postpartum preeclampsia or eclampsia: defining its place and management among the hypertensive disorders of pregnancy. Am J Obstet Gynecol. 2022;226(2S):S1211-S1221. PMID: 35177218
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Lu JF, Nightingale CH. Magnesium sulfate in eclampsia and pre-eclampsia: pharmacokinetic principles. Clin Pharmacokinet. 2000;38(4):305-314. PMID: 10803454
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Scott G, Gillon TE, Pels A, et al. Guidelines-similarities and dissimilarities: a systematic review of international clinical practice guidelines for pregnancy hypertension. Am J Obstet Gynecol. 2021;224(2S):S26-S37. PMID: 32828743
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Padda J, Khalid K, Colaco LB, et al. Efficacy of Magnesium Sulfate on Maternal Mortality in Eclampsia. Cureus. 2021;13(8):e17423. PMID: 34567870
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van Dijk MG, Díaz Olavarrieta C, Zuñiga PU, et al. Use of magnesium sulfate for treatment of pre-eclampsia and eclampsia in Mexico. Int J Gynaecol Obstet. 2013;121(3):268-271. PMID: 23465851
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Tranquilli AL, Brown MA, Zeeman GG, et al. The definition of severe and early-onset preeclampsia. Statements from the International Society for the Study of Hypertension in Pregnancy (ISSHP). Pregnancy Hypertens. 2013;3(1):44-47. PMID: 26105729
Common Exam Questions:
-
MRCP: "A 28-year-old primigravida at 32 weeks presents with BP 165/110, proteinuria, and epigastric pain. What is the most appropriate immediate management?"
- Answer: Admit, IV labetalol to control BP, magnesium sulfate for seizure prophylaxis, fluid restriction, urgent delivery planning
-
OSCE: "How would you manage a patient with severe pre-eclampsia?"
- Answer: ABC, IV access, BP control (labetalol/hydralazine), magnesium sulfate, fluid restriction (80ml/hr), continuous monitoring, delivery planning
-
MRCOG: "What are the diagnostic criteria for pre-eclampsia?"
- Answer: Hypertension ≥140/90 after 20 weeks + proteinuria (PCR ≥30) or end-organ dysfunction
-
MRCP: "A woman with pre-eclampsia develops seizures. What is the first-line treatment?"
- Answer: Magnesium sulfate 4g IV loading over 10-15 minutes, then 1g/hr infusion
-
OSCE: "What are the red flags in pre-eclampsia?"
- Answer: Severe hypertension, epigastric pain, visual disturbance, clonus, papilloedema, HELLP features
Viva Points:
Opening Statement:
"Pre-eclampsia is a multisystem disorder of pregnancy characterized by new-onset hypertension and proteinuria or end-organ dysfunction after 20 weeks gestation. It affects 2-8% of pregnancies and is a leading cause of maternal and perinatal morbidity and mortality. The condition results from abnormal placentation leading to endothelial dysfunction. The mainstay of treatment is blood pressure control, magnesium sulfate for seizure prophylaxis in severe cases, and delivery, which is the only definitive cure."
Key Facts to Mention:
- Incidence: 3-5% of pregnancies in developed countries
- Pathophysiology: Two-stage theory - poor placentation → placental ischaemia → endothelial dysfunction
- Key investigation: Urine protein:creatinine ratio (PCR ≥30 mg/mmol)
- First-line treatment: Labetalol for BP control, magnesium sulfate for severe disease
- Important complication: Eclampsia (seizures), HELLP syndrome
Classification to Quote:
- "Pre-eclampsia is classified as mild (BP 140-159/90-109) or severe (BP ≥160/110 or end-organ dysfunction)"
- "HELLP syndrome is a variant of severe pre-eclampsia characterized by Haemolysis, Elevated Liver enzymes, and Low Platelets"
Evidence to Cite:
- "The ASPRE trial (2017, n=1,776) showed aspirin 150mg from 11-14 weeks reduced preterm pre-eclampsia by 62% in high-risk women"
- "The Magpie trial (2002, n=10,141) confirmed magnesium sulfate reduces eclampsia risk by 58%"
- "NICE NG133 (2019) recommends BP target less than 135/85 and aspirin prophylaxis for high-risk women"
Structured Answer Framework:
-
Definition and Epidemiology (30 seconds)
- Define pre-eclampsia, mention incidence, risk factors
-
Aetiology and Pathophysiology (45 seconds)
- Two-stage theory, poor placentation, endothelial dysfunction
-
Clinical Features (45 seconds)
- Symptoms (headache, visual disturbance, epigastric pain), signs (hypertension, clonus), red flags
-
Investigations (30 seconds)
- Urine PCR, PlGF, FBC, LFTs, U&E
-
Management (60 seconds)
- BP control, magnesium sulfate, fluid restriction, delivery timing
-
Complications and Prognosis (30 seconds)
- Eclampsia, HELLP, stroke, long-term cardiovascular risk
Common Mistakes:
- ❌ Forgetting to mention red flags (epigastric pain, visual disturbance)
- ❌ Not knowing the diagnostic criteria (PCR ≥30 mg/mmol)
- ❌ Quoting outdated treatment (diazepam for eclampsia - wrong!)
- ❌ Missing key investigation (PlGF testing)
- ❌ Not knowing drug doses (magnesium sulfate 4g loading, 1g/hr)
- ❌ Forgetting fluid restriction (80ml/hr in severe disease)
- ❌ Not mentioning delivery as definitive cure
Dangerous Errors to Avoid:
- ⚠️ Using ACE inhibitors/ARBs (teratogenic, cause renal failure in fetus)
- ⚠️ Giving normal fluid rates in severe disease (causes pulmonary oedema)
- ⚠️ Delaying delivery inappropriately when severe
- ⚠️ Missing eclampsia risk (clonus >3 beats)
Outdated Practices (Do NOT mention):
- Salt restriction - No longer recommended, not helpful
- Bed rest - Not proven beneficial, may increase thrombosis risk
- Diuretics - Not recommended, patients are volume contracted
- Diazepam for eclampsia - Magnesium sulfate is first-line
Examiner Follow-Up Questions:
-
"What would you do if a patient develops eclampsia?"
- Answer: Secure airway, give magnesium sulfate 4g IV loading, then 1g/hr infusion, control BP, deliver urgently
-
"What is the evidence for aspirin prophylaxis?"
- Answer: ASPRE trial (2017) showed 62% reduction in preterm pre-eclampsia with aspirin 150mg from 11-14 weeks in high-risk women
-
"How would you manage HELLP syndrome?"
- Answer: Urgent delivery (usually CS), supportive care, may need blood products, close monitoring for complications
-
"What are the contraindications to labetalol?"
- Answer: Asthma (beta-blocker effect), heart block, severe bradycardia
-
"When would you deliver a patient with pre-eclampsia?"
- Answer: Severe disease at any gestation (after stabilization), mild disease at 37 weeks, or earlier if deteriorating or fetal compromise
Conditions to Consider
Pre-eclampsia must be distinguished from other causes of hypertension in pregnancy and from conditions that mimic its complications:
| Condition | Key Distinguishing Features | Investigation | Management Difference |
|---|---|---|---|
| Chronic hypertension | HTN present less than 20 weeks or pre-pregnancy | BP record, no proteinuria | Continue safe antihypertensives |
| Gestational hypertension | HTN >20 weeks, NO proteinuria/organ dysfunction | No proteinuria | Monitor, may progress to PET |
| HELLP syndrome | Hemolysis, elevated LFTs, low platelets | LFTs, blood film, platelets | Urgent delivery |
| Acute fatty liver of pregnancy | Jaundice, hypoglycemia, coagulopathy | LFTs, glucose, coagulation | Urgent delivery, ICU |
| TTP/HUS | Microangiopathic hemolytic anemia, fever, neuro signs | Blood film, ADAMTS13 | Plasmapheresis |
| SLE flare | Known SLE, joint pain, rash | Anti-dsDNA, complement | Immunosuppression |
| Pheochromocytoma | Episodic HTN, sweating, palpitations | Urinary metanephrines | Alpha-blockade, surgery |
Pre-eclampsia vs. Chronic Hypertension
Clinical Challenge:
- Both present with elevated BP in pregnancy
- Key Difference: Timing and presence of proteinuria/organ dysfunction
| Feature | Pre-eclampsia | Chronic Hypertension |
|---|---|---|
| Onset | >20 weeks | less than 20 weeks or pre-pregnancy |
| Proteinuria | Present (≥30 mg/mmol PCR) | Absent (unless superimposed PET) |
| Platelets | May be low (less than 100) | Normal |
| LFTs | May be elevated (ALT >40) | Normal |
| PlGF | Low (less than 100 pg/ml) | Normal |
| Symptoms | Headache, visual disturbance, epigastric pain | Usually asymptomatic |
| Fetal growth | May be restricted | Usually normal |
| Management | Monitor, may need delivery | Continue antihypertensives |
Superimposed Pre-eclampsia:
- Definition: Pre-eclampsia developing in woman with chronic HTN
- Clues: New proteinuria, rising BP, low platelets, or symptoms
- Higher risk: More severe disease, earlier onset
- Management: As for pre-eclampsia
Pre-eclampsia vs. HELLP Syndrome
Relationship:
- HELLP is a severe variant/complication of pre-eclampsia
- 10-20% of severe pre-eclampsia develops HELLP
- HELLP can occur without hypertension or proteinuria (10-15% of cases)
| Feature | Pre-eclampsia | HELLP Syndrome |
|---|---|---|
| Hypertension | Present (≥140/90) | May be absent (10-15%) |
| Proteinuria | Present | May be absent |
| Hemolysis | Absent | Present (LDH >600, bilirubin >20) |
| Elevated LFTs | May be present (ALT >40) | Marked (AST/ALT >70) |
| Low platelets | May be present (less than 100) | Present (less than 100, often less than 50) |
| Symptoms | Headache, visual disturbance | RUQ pain, nausea/vomiting |
| Urgency | Deliver at term or if severe | Urgent delivery (within 24-48h) |
Tennessee Classification of HELLP:
- Class 1 (severe): Platelets less than 50, AST >70, LDH >600
- Class 2 (moderate): Platelets 50-100, AST >70, LDH >600
- Class 3 (mild): Platelets 100-150, AST >40, LDH >600
Pre-eclampsia vs. Acute Fatty Liver of Pregnancy (AFLP)
Clinical Challenge:
- Both present with elevated LFTs, coagulopathy, and may have hypertension
- Key Difference: AFLP has hypoglycemia, jaundice, and severe coagulopathy
| Feature | Pre-eclampsia/HELLP | Acute Fatty Liver of Pregnancy |
|---|---|---|
| Hypertension | Present (usually) | May be present |
| Jaundice | Absent | Present (bilirubin >100) |
| Hypoglycemia | Absent | Present (less than 4 mmol/L) |
| Coagulopathy | May be present (mild) | Severe (PT >15s, fibrinogen less than 2) |
| Platelets | May be low | Low |
| Encephalopathy | Absent (unless eclampsia) | Present (hepatic encephalopathy) |
| Imaging | Normal liver | Bright liver on CT, fat on biopsy |
| Management | Deliver urgently | Deliver urgently, ICU, may need transplant |
Swansea Criteria for AFLP (≥6 in absence of other explanation):
- Vomiting, abdominal pain, polydipsia/polyuria, encephalopathy
- Elevated bilirubin (>14), hypoglycemia (less than 4), urate (>340), WCC (>11)
- Ascites, bright liver on CT, microvesicular steatosis on biopsy
"Can't Miss" Diagnoses
1. Eclampsia:
- Clue: Tonic-clonic seizure in pregnant/postpartum woman with pre-eclampsia
- Key: Can occur without warning (40% of eclampsia has NO prior symptoms)
- Investigation: Clinical diagnosis, don't delay treatment
- Management: Airway, magnesium sulfate 4g IV, BP control, urgent delivery
2. Stroke/Intracerebral Hemorrhage:
- Clue: Severe headache, focal neurology, very high BP (>160/110)
- Key: Leading cause of maternal death in pre-eclampsia
- Investigation: CT head (urgent)
- Management: BP control (target less than 140/90), neurosurgical input, may need delivery
3. Placental Abruption:
- Clue: Abdominal pain, vaginal bleeding, fetal distress
- Key: 2-3x more common in pre-eclampsia
- Investigation: Clinical, CTG (fetal distress), USS may show
- Management: Urgent/emergency delivery
4. Pulmonary Edema:
- Clue: Breathlessness, crackles, hypoxia
- Key: Due to fluid overload (if normal IV fluids given) or cardiac dysfunction
- Investigation: CXR, Echo
- Management: Fluid restriction, oxygen, diuretics, may need delivery
Primary Prevention (Preventing Pre-eclampsia)
Primary prevention focuses on reducing the risk of developing pre-eclampsia in at-risk women:
| Strategy | Target Population | Evidence Level | Effectiveness |
|---|---|---|---|
| Aspirin 150mg | High-risk women from 12 weeks | 1A | 62% reduction in preterm PET |
| Calcium supplementation | Low dietary calcium intake (less than 600mg/day) | 1A | 55% reduction in PET |
| Weight optimization | Obese women (pre-pregnancy) | Moderate | May reduce risk |
| Smoking cessation | All pregnant women | High | Reduces all complications |
Aspirin Prophylaxis (CRITICAL):
High-Risk Factors (≥1 requires aspirin):
- Previous pre-eclampsia
- Chronic hypertension
- Chronic kidney disease
- Diabetes (type 1 or 2)
- Autoimmune disease (SLE, APS)
Moderate-Risk Factors (≥2 requires aspirin):
- First pregnancy
- Age ≥40 years
- BMI ≥35
- Family history of pre-eclampsia
- Multiple pregnancy
- Interval >10 years since previous pregnancy
Aspirin Protocol:
- Dose: 150mg daily (at night)
- Start: 12 weeks gestation (ideally before 16 weeks)
- Stop: 36 weeks or delivery
- Evidence: ASPRE trial (2017) - 62% reduction in preterm pre-eclampsia
Calcium Supplementation:
- Indication: Low dietary calcium (less than 600mg/day), especially in low-income countries
- Dose: 1.5-2g elemental calcium daily
- Evidence: WHO recommends in low-calcium populations
- Effect: 55% reduction in pre-eclampsia, 45% reduction in severe PET
Pre-Pregnancy Optimization:
- Weight loss: If BMI >30, encourage weight loss before conception
- Optimize chronic conditions: Hypertension, diabetes control
- Review medications: Stop ACE-I/ARB (teratogenic), switch to safe alternatives
- Folic acid: 5mg daily if high-risk (previous PET, diabetes, obesity)
Secondary Prevention (Early Detection & Management)
For women at risk or with early signs of pre-eclampsia, close monitoring enables early intervention:
1. Antenatal Monitoring in High-Risk Women:
| Risk Level | Monitoring Frequency | Investigations | Intervention Threshold |
|---|---|---|---|
| High-risk (on aspirin) | Every 2-3 weeks from 20 weeks | BP, urinalysis, PlGF if symptoms | New HTN or proteinuria |
| Previous severe PET | Every 2 weeks from 20 weeks | BP, urinalysis, growth scans | As above |
| Chronic HTN | Every 2-4 weeks | BP, urinalysis, renal function | New proteinuria or symptoms |
2. PlGF (Placental Growth Factor) Testing:
Indications for PlGF Test (20-35 weeks):
- Suspected pre-eclampsia (new HTN or proteinuria)
- Monitoring high-risk women with symptoms
Interpretation:
| PlGF Level | Interpretation | Action |
|---|---|---|
| less than 100 pg/ml | High risk PET within 14 days | Increased surveillance, plan delivery |
| 100-150 pg/ml | Intermediate risk | Repeat in 1 week, close monitoring |
| >150 pg/ml | Low risk PET within 14 days | Reassure, routine care |
Evidence: PARROT trial (2019) - PlGF-guided care reduces severe maternal outcomes by 20%
3. Early Management of Mild Pre-eclampsia:
Goal: Prolong pregnancy safely to term while monitoring for progression
Monitoring:
- BP: Twice weekly (home monitoring acceptable if less than 150/100)
- Urinalysis: Weekly (or if symptoms)
- Bloods: Weekly (FBC, LFTs, renal function)
- Fetal monitoring: Growth scans every 2 weeks, CTG if less than 37 weeks
Indications for Increased Surveillance/Delivery:
- Progression to severe PET (BP ≥160/110, symptoms, platelets less than 100, ALT >70)
- Fetal growth restriction
- Abnormal Dopplers (high resistance)
- Maternal symptoms (headache, visual disturbance, epigastric pain)
Tertiary Prevention (Preventing Recurrence)
For women who have had pre-eclampsia, preventing recurrence in future pregnancies:
Recurrence Risk:
| Previous PET Severity | Recurrence Risk | Management |
|---|---|---|
| Mild PET at term | 10-15% | Aspirin 150mg from 12 weeks |
| Severe PET less than 34 weeks | 25-40% | Aspirin, close monitoring, early delivery planning |
| Severe PET less than 28 weeks | 40-50% | Aspirin, specialist antenatal care, consider delivery less than 37 weeks |
| HELLP syndrome | 20-25% | Aspirin, close monitoring for HELLP recurrence |
Pre-Pregnancy Counseling:
Review Previous Pregnancy:
- When did PET develop? (Earlier onset = higher recurrence risk)
- How severe? (HELLP, delivery less than 34 weeks = higher risk)
- Fetal outcomes? (Stillbirth, IUGR = higher risk)
- Postpartum recovery? (Persistent HTN?)
Optimize Risk Factors:
- Weight loss: If BMI >30
- Control chronic HTN: Target less than 140/90 pre-pregnancy
- Diabetes control: HbA1c less than 6.5%
- Autoimmune disease: Optimize control (SLE, APS)
- Medication review: Stop ACE-I/ARB, start safe alternatives
Aspirin Protocol:
- All women with previous PET: Aspirin 150mg from 12 weeks
- Previous severe PET: Consider earlier start (from 8-10 weeks in some centers)
Enhanced Surveillance:
- Booking: Early (8-10 weeks), discuss risks, start aspirin
- 20 weeks: BP, urinalysis, PlGF baseline
- 24 weeks onwards: BP and urinalysis every 2 weeks
- Growth scans: Every 3-4 weeks from 24 weeks
- PlGF testing: If any symptoms or signs
Delivery Planning:
- Mild PET: Aim for 37 weeks
- Previous severe PET less than 34 weeks: Discuss elective delivery at 36-37 weeks
- Previous HELLP: Close monitoring from 32 weeks, deliver 36-37 weeks
Long-Term Cardiovascular Risk:
- Increased risk: Women with previous PET have 2-4x risk of future CVD
- Screening: Annual BP check, lipid profile at 40 years
- Lifestyle: Encourage healthy diet, exercise, weight management
- Statins: May be indicated if high cardiovascular risk
Women with Chronic Hypertension
Specific Considerations:
- Higher risk: 20-25% develop superimposed pre-eclampsia
- Difficult diagnosis: Hard to distinguish superimposed PET from worsening chronic HTN
- Medication: Need safe antihypertensives in pregnancy
Pre-Pregnancy Management:
Medication Review (CRITICAL):
| Current Medication | Pregnancy Safety | Action |
|---|---|---|
| ACE-I/ARB | Contraindicated (teratogenic, renal failure) | STOP - switch to labetalol/nifedipine |
| Thiazide diuretics | Generally avoided | STOP - switch to safer alternative |
| Atenolol | Avoid (growth restriction) | STOP - switch to labetalol |
| Labetalol | Safe | Continue |
| Nifedipine MR | Safe | Continue |
| Methyldopa | Safe (but sedating) | Can use |
Target BP Pre-Pregnancy: less than 140/90
Pregnancy Management:
First Trimester:
- BP typically falls: May need to reduce/stop medications (BP can drop to 100-110/60-70)
- Monitor closely: Weekly BP checks
- Aspirin: 150mg from 12 weeks (ALL women with chronic HTN)
Second/Third Trimester:
- BP typically rises: May need to increase medications from 20 weeks
- Monitor for superimposed PET: Check urinalysis, bloods fortnightly
- PlGF testing: Low threshold if any symptoms
Diagnosis of Superimposed Pre-eclampsia:
In woman with chronic HTN, diagnose superimposed PET if:
- New proteinuria: PCR ≥30 mg/mmol
- Sustained rise in BP: Increase by 30/20 mmHg
- Thrombocytopenia: Platelets less than 100
- Elevated LFTs: ALT >70
- Symptoms: Headache, visual disturbance, epigastric pain
- Low PlGF: less than 100 pg/ml
Delivery Planning:
- Well-controlled chronic HTN, no superimposed PET: Deliver 37-38 weeks
- Superimposed PET: Deliver 34-37 weeks depending on severity
Women with Diabetes (Type 1, Type 2, Gestational)
Specific Considerations:
- Higher risk: Diabetes increases PET risk 2-4x
- Earlier onset: Often develops earlier (less than 34 weeks)
- Worse outcomes: Higher risk of severe PET, HELLP, stillbirth
Risk by Diabetes Type:
| Type | PET Risk | Management |
|---|---|---|
| Type 1 diabetes | 15-20% | Aspirin, close monitoring, early delivery (37-38 weeks) |
| Type 2 diabetes | 15-20% | Aspirin, close monitoring, early delivery (37-38 weeks) |
| Gestational diabetes | 10-15% | Aspirin if other risk factors, monitor closely |
Pre-Pregnancy (Type 1/2):
- Optimize control: Target HbA1c less than 6.5% (ideally less than 48 mmol/mol)
- Retinopathy screening: Refer ophthalmology (pregnancy can worsen diabetic retinopathy)
- Nephropathy screening: Urine PCR, creatinine (baseline for later comparison)
- Aspirin: 150mg from 12 weeks
- High-dose folic acid: 5mg daily
Pregnancy Management:
- Tight glycemic control: Reduces PET risk
- Enhanced surveillance: BP and urinalysis every 2 weeks from 20 weeks
- Growth scans: Every 3-4 weeks (diabetes + PET increases IUGR risk)
- Baseline proteinuria: If pre-existing diabetic nephropathy, use change from baseline to diagnose PET
Delivery Timing:
- Uncomplicated diabetes, no PET: 38-39 weeks
- Diabetes + mild PET: 37 weeks
- Diabetes + severe PET: 34-37 weeks depending on severity
Women with Chronic Kidney Disease
Specific Considerations:
- Very high risk: 30-50% develop pre-eclampsia if CKD stage 3-5
- Diagnostic challenge: Pre-existing proteinuria makes PET diagnosis difficult
- Worsening renal function: Pregnancy can worsen CKD
- Higher maternal/fetal risk: Increased risk of severe PET, preterm delivery, stillbirth
Pre-Pregnancy Counseling:
Risk Stratification by CKD Stage:
| CKD Stage | eGFR (ml/min) | PET Risk | Pregnancy Recommendation |
|---|---|---|---|
| Stage 1-2 | >60 | 20-30% | Generally safe, close monitoring |
| Stage 3 | 30-59 | 30-50% | High risk, specialist care |
| Stage 4-5 | less than 30 | >50% | Very high risk, consider deferring pregnancy |
Baseline Investigations:
- Creatinine: Baseline (will increase in pregnancy)
- Proteinuria: Baseline PCR (use change from baseline to diagnose PET)
- BP: Optimize pre-pregnancy (less than 140/90)
- Medication review: Stop ACE-I/ARB (may have been used for renal protection)
Pregnancy Management:
- Aspirin: 150mg from 12 weeks (CRITICAL - very high risk)
- Enhanced surveillance: BP, urinalysis, renal function every 2 weeks
- Diagnosis of PET: Difficult if pre-existing proteinuria
- Use sustained increase in proteinuria (doubling of PCR)
- Or low PlGF (less than 100)
- Or symptoms + rising BP
- Delivery planning: 34-37 weeks if PET develops, 37-38 weeks if uncomplicated
Postpartum:
- Renal function: Monitor closely (may take 6-12 weeks to return to baseline)
- BP: Often remains elevated, may need long-term treatment
- Contraception: Progesterone-only methods safe (avoid estrogen if HTN)
Women with Autoimmune Disease (SLE, APS)
Specific Considerations:
- Very high risk: SLE increases PET risk 3-5x, APS 5-10x
- Diagnostic challenge: SLE flare can mimic PET (proteinuria, thrombocytopenia, HTN)
- Fetal risk: Increased risk of IUGR, stillbirth
- Medication: Need safe immunosuppression
Systemic Lupus Erythematosus (SLE):
Pre-Pregnancy:
- Quiescent disease: Wait 6-12 months of stable disease before conception
- Medication optimization:
- Safe: Hydroxychloroquine, azathioprine, prednisolone (less than 20mg)
- Avoid: Methotrexate, mycophenolate (teratogenic)
- Baseline serology: Anti-Ro, anti-La, anti-dsDNA, complement (C3, C4)
- Aspirin + LMWH: If positive aPL antibodies
Pregnancy Management:
- Continue hydroxychloroquine: Reduces flare risk and PET risk
- Monitor disease activity: Anti-dsDNA, complement every 4-8 weeks
- Distinguish SLE flare from PET:
| Feature | SLE Flare | Pre-eclampsia |
|---|---|---|
| Proteinuria | Present | Present |
| Thrombocytopenia | Present | Present |
| Hypertension | May be present | Present |
| Anti-dsDNA | Rising | Normal/stable |
| Complement (C3, C4) | Falling | Normal/rising |
| PlGF | Normal | Low |
| Renal biopsy | Lupus nephritis | FSGS pattern |
Antiphospholipid Syndrome (APS):
Pre-Pregnancy:
- Confirm diagnosis: aPL antibodies positive on 2 occasions, 12 weeks apart
- Aspirin + LMWH: Start as soon as pregnancy confirmed
Pregnancy Management:
- Aspirin 150mg: From conception
- LMWH: Prophylactic dose (enoxaparin 40mg SC daily or dalteparin 5000 units SC daily)
- Enhanced surveillance: Weekly BP and urinalysis from 20 weeks
- Growth scans: Fortnightly from 24 weeks
- Delivery: 37-38 weeks
Pregnant Women with Obesity (BMI ≥30)
Specific Considerations:
- Increased risk: BMI ≥35 increases PET risk 3-4x
- Technical challenges: BP measurement (need large cuff), USS imaging difficult
- Comorbidities: Often have chronic HTN, diabetes
Pre-Pregnancy:
- Weight loss: Encourage before conception (reduces PET risk)
- Bariatric surgery: Consider if BMI >40 (wait 12-18 months post-surgery before pregnancy)
- Optimize comorbidities: Treat HTN, diabetes
Pregnancy Management:
- Aspirin: 150mg from 12 weeks (BMI ≥35 is moderate risk factor)
- BP monitoring: Use appropriate-sized cuff (bladder width ≥40% arm circumference)
- Mobility: Encourage gentle exercise (reduces complications)
- VTE prophylaxis: Consider if BMI ≥40
- Delivery planning:
- Higher risk of cesarean section (if BMI >40, 50% CS rate)
- Anesthetic review in third trimester
Teenage Pregnancy (less than 20 years)
Specific Considerations:
- Higher risk: Teenage pregnancy increases PET risk 2x (especially if less than 16 years)
- Socioeconomic factors: Often associated with poverty, poor nutrition, smoking
- Delayed presentation: May not engage with antenatal care early
Management:
- Early engagement: Ensure booking by 10 weeks
- Aspirin: 150mg from 12 weeks if first pregnancy
- Enhanced support: Social support, ensure compliance with antenatal care
- Smoking cessation: Critical (reduces PET and IUGR risk)
Multiple Pregnancy (Twins, Triplets)
Specific Considerations:
- Higher risk: Twin pregnancy increases PET risk 2-3x, triplets 3-4x
- Earlier onset: Often develops earlier (less than 34 weeks)
- Worse outcomes: Higher risk of severe PET, preterm delivery
Management:
- Aspirin: 150mg from 12 weeks (ALL multiple pregnancies)
- Enhanced surveillance: BP and urinalysis every 2 weeks from 20 weeks
- Growth scans: Every 2 weeks from 20 weeks
- Delivery planning:
- Uncomplicated twins: 37-38 weeks
- Twins + PET: 34-37 weeks
- Triplets: Deliver 32-34 weeks regardless of PET
Last Reviewed: 2025-12-24 | MedVellum Editorial Team
Medical Disclaimer: MedVellum content is for educational purposes and clinical reference. Clinical decisions should account for individual patient circumstances. Always consult appropriate specialists and current guidelines.